Circulating levels of phthalate metabolites are associated with prevalent diabetes
in the elderly.

Abstract

OBJECTIVEPhthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome
proliferator-activated receptors (PPARs). Because PPAR-γ agonists modulate insulin
sensitivity and are used to treat type 2 diabetes, we investigated whether circulating
levels of phthalate metabolites are related to prevalent type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation
of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected
in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer.
Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a
fasting plasma glucose >7.0 mmol/L.RESULTSA total of 114 subjects were shown to have diabetes. Following adjustment for sex,
BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise
habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01),
monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05),
but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence
of diabetes. Using the fasting proinsulin-to-insulin ratio as a marker of insulin
secretion and the homeostasis model assessment-insulin resistance index as a marker
of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas
MEP and MMP mainly were related to insulin resistance.CONCLUSIONSThe findings in this cross-sectional study showed that several phthalate metabolites
are related to diabetes prevalence, as well as to markers of insulin secretion and
resistance. These findings support the view that these commonly used chemicals might
influence major factors that are regulating glucose metabolism in humans at the level
of exposure of phthalate metabolites seen in the general elderly population.